PROJECT SUMMARY/ ABSTRACT Human pancreatic islets are an essential research resource allowing for the translation of fundamental questions related to the prevention, treatment, and pathophysiology of diabetes mellitus. Recent data has highlighted important differences between islets from animal models and human islets, substantiating the continued need for researcher access to human islets. However, several challenges exist in maintaining and enhancing the necessary infrastructure and coordinating function to effectively and efficiently distribute this precious resource to islet research laboratories. City of Hope (COH) is applying for this UC4 renewal to remain the Coordinating Center (CC) to support the Integrated Islet Distribution Program (IIDP) that provides for the distribution of human cadaveric islets for biomedical research to researchers worldwide. Our proposal leverages the significant investment made by NIH over the last 12 years that has established and successfully maintained this islet distribution network at COH. From qualification and auditing of high-quality suppliers to forecasting, tracking, and meeting the needs of investigators, our experienced IIDP-CC team has worked with 19 different isolation laboratories to coordinate the distribution of over 231 million islet equivalents to 316 investigative studies over a period of more than 14 years, facilitating the completion of 499 publications. As the ongoing IIDP-CC, we will continue to subcontract with qualified islet isolation facilities to prepare and distribute human islets through our advanced electronic Islet Allocation System. As the IIDP-CC, we will continue to manage the review process for IIDP applications to establish investigator eligibility for islet receipt (including opportunity pool submissions), maintain investigator rosters, and further enhance our IAS that allows distribution centers to broadcast offers online and notifies approved waiting researchers of islet availability. We will continue to maintain the existing cost recovery system through subscription fees collected from islet researchers, which has successfully garnered approximately $3,000,000 under the existing grant to offset the expenses of pancreatic processing. We will continue to closely monitor and help to improve the quality of islets distributed, through the continuation of a Quality Control Core Facility that tests a sample from each islet isolation using agreed upon quality control assays. Quality control data, as well as extensive donor and islet isolation data, will be made available to approved investigators through online access. Through our proven state-of-the-art administrative, business, technical, statistical, quality assurance, and informatics processes and tools, this project will benefit from COH?s advanced systems, and the accessibility of human islets for investigators conducting essential diabetes mellitus research will be secured. Through the aims described in this proposal, we will provide an indispensable research resource for the diabetes research community by ensuring that the IIDP network remains stable, technologically advanced, continually enhanced, and fully responsive to the islet needs of the research community, thus promoting the next generation of scientific experimentation toward prevention and treatment of diabetes.